Retrograde activation of presynaptic NMDA receptors enhances GABA release at cerebellar interneuron–Purkinje cell synapses

Activity of neurons in the dorsal motor nucleus of the vagus nerve (DMV) is closely regulated by synaptic input, and regulation of that input by glutamate receptors on presynaptic terminals has been proposed. Presynaptic N-methyl-d-aspartic acid (NMDA) receptors have been identified in a number of brain regions and act to modulate neurotransmitter release, but functional presynaptic NMDA receptors have not been adequately studied in the DMV. This study identified the presence and physiological function of presynaptic NMDA receptors on synaptic input to DMV neurons. Whole-cell patch-clamp recordings from DMV neurons in acute slices from mice revealed prevalent miniature excitatory postsynaptic currents, which were significantly increased in frequency, but not amplitude, by application of NMDA. Antagonism of NMDA receptors with dl-2-amino-5-phosphonopentanoic acid (100 μM) resulted in a decrease in miniature excitatory postsynaptic current frequency and an increase in the paired pulse ratio of responses following afferent stimulation. No consistent effects of presynaptic NMDA receptor modulation were observed on GABAergic inputs. These results suggest that presynaptic NMDA receptors are present in the dorsal vagal complex and function to facilitate the release of glutamate, preferentially onto DMV neurons tonically, with little effect on GABA release. This type of presynaptic modulation represents a potentially novel form of glutamate regulation in the DMV, which may function to regulate glutamate-induced activity of central parasympathetic circuits.

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Presynaptic NMDA receptors cooperate with local action potentials to implement activity-dependent GABA release from the reciprocal olfactory bulb granule cell spine

10.1101/440198 ◽

2018 ◽

Cited By ~ 2

Author(s):

Vanessa Lage-Rupprecht ◽

Li Zhou ◽

Gaia Bianchini ◽

S. Sara Aghvami ◽

Max Mueller ◽

...

Keyword(s):

Olfactory Bulb ◽

Nmda Receptors ◽

Granule Cells ◽

Specific Activity ◽

Sensory System ◽

Gaba Release ◽

Cooperative Action ◽

Two Photon ◽

Presynaptic Nmda Receptors ◽

Activity Dependent

AbstractIn the rodent olfactory bulb the smooth dendrites of the principal glutamatergic mitral cells (MCs) form reciprocal dendrodendritic synapses with large spines on GABAergic granule cells (GC), where unitary release of glutamate can trigger postsynaptic local activation of voltage-gated Na+-channels (Navs), i.e. a spine spike. Can such single MC input evoke reciprocal release? We find that unitary-like activation via two-photon uncaging of glutamate causes GC spines to release GABA both synchronously and asynchronously onto MC dendrites. This release indeed requires activation of Navs and high-voltage-activated Ca2+-channels (HVACCs), but also of NMDA receptors (NMDAR). Simulations show temporally overlapping HVACC- and NMDAR-mediated Ca2+-currents during the spine spike, and ultrastructural data prove NMDAR presence within the GABAergic presynapse. This cooperative action of presynaptic NMDARs allows to implement synapse-specific, activity-dependent lateral inhibition and thus could provide an efficient solution to combinatorial percept synthesis in a sensory system with many receptor channels.

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Faculty Opinions recommendation of Postsynaptic, not presynaptic NMDA receptors are required for spike-timing-dependent LTD induction.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726494084.793520734 ◽

2016 ◽

Author(s):

Jeffry Isaacson

Keyword(s):

Nmda Receptors ◽

Spike Timing ◽

Presynaptic Nmda Receptors

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Physiological Properties of Late Inspiratory Neurons and Their Possible Involvement in Inspiratory Off-Switching in Cats

Journal of Neurophysiology ◽

10.1152/jn.00470.2001 ◽

2002 ◽

Vol 87 (2) ◽

pp. 1057-1067 ◽

Cited By ~ 29

Author(s):

Akira Haji ◽

Mari Okazaki ◽

Hiromi Yamazaki ◽

Ryuji Takeda

Keyword(s):

Nmda Receptors ◽

Gaba Release ◽

Membrane Depolarization ◽

Inhibitory Neurons ◽

Acid Decarboxylase ◽

Postsynaptic Potentials ◽

Inspiratory Neurons ◽

Small Constant ◽

Physiological Properties ◽

Decerebrate Cats

To assess the functional significance of late inspiratory (late-I) neurons in inspiratory off-switching (IOS), membrane potential and discharge properties were examined in vagotomized, decerebrate cats. During spontaneous IOS, late-I neurons displayed large membrane depolarization and associated discharge of action potentials that started in late inspiration, peaked at the end of inspiration, and ended during postinspiration. Depolarization was decreased by iontophoresis of dizocilpine and eliminated by tetrodotoxin. Stimulation of the vagus nerve or the nucleus parabrachialis medialis (NPBM) also evoked depolarization of late-I neurons and IOS. Waves of spontaneous chloride-dependent inhibitory postsynaptic potentials (IPSPs) preceded membrane depolarization during early inspiration and followed during postinspiration and stage 2 expiration of the respiratory cycle. Iontophoresed bicuculline depressed the IPSPs. Intravenous dizocilpine caused a greatly prolonged inspiratory discharge of the phrenic nerve (apneusis) and suppressed late-inspiratory depolarization as well as early-inspiratory IPSPs, resulting in a small constant depolarization throughout the apneusis. NPBM or vagal stimulation after dizocilpine produced small, stimulus-locked excitatory postsynaptic potentials (EPSPs) in late-I neurons. Neurobiotin-labeled late-I neurons revealed immunoreactivity for glutamic acid decarboxylase as well as N-methyl-d-aspartate (NMDA) receptors. These results suggest that late-I neurons are GABAergic inhibitory neurons, while the effects of bicuculline and dizocilpine indicate that they receive periodic waves of GABAergic IPSPs and glutamatergic EPSPs. The data lead to the conclusion that late-I neurons play an important inhibitory role in IOS. NMDA receptors are assumed to augment and/or synchronize late-inspiratory depolarization and discharge of late-I neurons, leading to GABA release and consequently off-switching of bulbar inspiratory neurons and phrenic motoneurons.

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